1. Field of the Invention
The invention relates to a method for the treatment of biological tissue of animal and human origin, such as porcine heart valves, heart valves of bovine pericardium or human cadaver heart valves, and biological tissue treated accordingly.
2. Background Art
With regard to the background of the invention it is to be stated that operation methods with an application of differently pre-treated biological tissue of animal origin, as collagen matrices, in particular in the course of tissue engineering, are gaining in importance in various surgical areas for future, improved therapy methods. Relevant application areas are to be seen in cardiovascular surgery, but orthopaedics and neurosurgery are also conceivable as areas of use.
For the application of collagen matrices in cardiovascular surgery, good blood compatibility and mechanical stability have to be ensured. As an example, in this context, heart valves of animal origin, such as porcine valves or valves of bovine pericardium are to be mentioned just as much as biological vessel prostheses with small diameters and pump chambers of biological or mechanical blood pumps. In orthopaedic surgical treatments, stable collagen matrices especially are of particular interest for the replacement of cartilage, ligaments and tendons. In neurosurgery, finally, a collagen tissue for closing the cranium, for example after tumour operations is to be regarded as an area of use of the present invention.
The special problems, on which the invention is based, are to be made clear from the example of replacement heart valves. Thus of the replacement heart valves implanted in over 200,000 patients a year worldwide about 50% are made from artificial, mechanical heart valves and 50% from biological implants based on porcine heart valves and valves from bovine pericardium. The implantation of mechanical heart valves, for permanent after-care, requires the administration of blood clotting-inhibiting medications, to avoid embolisms coming from the prostheses. Thus, patients attended to in this manner become virtually “artificial haemophiliacs”.
Biological heart valves of animal origin have the problem that they have to be treated with glutaraldehyde to achieve long-term stability. Owing to the free aldehyde groups thus being produced from glutardialdehyde, the biological heart valves have a toxic effect per se and can therefore not be colonised with cells. A cell colonisation should make these biovalves durable for significantly longer. However, a detoxification would be necessary before a cell colonisation. Medical studies are known in this context from the prior art, in which substances are used which bind free aldehyde groups. Reference is made in this context to the following literature references:
Gott J. P., Chih P., Dorsey L., Jay J. L., Jett G. K., Schoen F. J., Girardot J. M., Guyton R. A. “Calcification of porcine valves: a successful new method of antimineralisation” in Ann Thorac Surg 1992; 53: 207-216; Jones M., Eidbo E. E., Hilbert S. L., Ferrans V. J., Clarck R. E. “Anticalcification treatments of bioprosthetic heart valves: in vivo studies in sheep” in J Cardiovasc Surg 1989; 4: 69-73; Grabenwöger M., Sider J., Fitzal F., Zelenka C., Windberger U., Grimm M. “Impact of glutaraldehyde on calcification of pericardial bioprosthetic heart valve material” in Ann Thorac Surg 1996; 62: 772-7 and finally Webb C. L., Benedict J. J., Schoen F. J., Linden J. A., Levy R. J. “Inhibition of bioprosthetic valve calcification with aminodiphosphonate covalently bound material to residual aldehyde groups” in Ann Thorac Surg 1988; 46: 309-16.
Furthermore, tests were carried out to achieve a detoxification with the aid of citric acid. This was partially successful as disclosed in Gulbins H., Goldemund A., Anderson I., Haas U., Uhlig A., Meiser B., Reichart B. “Preseeding with autologous fibroblasts improves endothelialisation of glutaraldehyde-fixed porcine aortic valves” in J Thorac Cardiovasc Surg 2003; 125: 592-601.
The degrees of detoxification achieved there were merely 20 to 30%.
With a suitable detoxification of the tissue fixed with glutaraldehyde and corresponding coatability by the body's own tissue after the implantation—so-called “endothelialisation” —it was possible to achieve the goal of a heart valve which could last for life without the administration of medications to inhibit blood clotting.
A further example of the scope of the present invention is small-bore vessel prostheses. Implants of this type are generally currently made of plastics material, namely PTFE or PET. They have a comparatively high closure rate, in particular in their application as a vessel replacement for peripheral leg vessels, aortocoronary bypasses and peripheral dialysis shunts. The consequences of vessel closures in these prosthesis regions are drastic, including leg amputation, myocardial infarction resulting in death or the necessity of a shunt revision. Here, too, small-bore glutaraldehyde-fixed biological tissue of animal origin in the form of porcine, bovine or goat donor vessels could bring a substantial improvement if tissue of this type could be detoxified and endothelialised, or is endothelialised in the bloodstream. In the application of muscular pumps, as well, thromboembolism complications could be avoided if the components coming into contact with the blood could be increased with regard to their biocompatibility, for example through suitable detoxification measures.
Further application areas of biological tissue of this type in the form of collagen matrices of animal origin may be stable and biocompatible glutaraldehyde-fixed and detoxified biological tissue for the treatment of osteoarthritis of the hip, knee and ankle joints. Furthermore, further applications to close the cranium after injuries or tumour operations with the aid of a correspondingly glutaraldehyde-fixed and detoxified bovine pericardium as a cerebro-protective application are just as conceivable as applications, for example, in thorax surgery as the thorax wall or diaphragm replacement, in abdominal surgery for abdominal wall replacement or in the ENT area as an eardrum replacement.